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Background Prader-Willi syndrome (PWS) is a genetic disorder associated with intellectual disabilities, compulsivity, hyperphagia and increased risks of life-threatening obesity. Food preferences in people with PWS are well documented, but research has yet to focus on other properties of food in PWS, including composition and suitability for consumption. It is also unclear how food perceptions differ across the two major genetic subtypes of PWS. Methods This study examined neural responses to food stimuli in 17 adults with PWS, nine with paternal deletions and eight with maternal uniparental disomy (UPD), and in nine age-matched typical controls. Visual event-related potentials (ERPs) were recorded in response to food images varying in food composition and suitability for consumption during a passive viewing paradigm. Results Group differences were observed for the N1 and P3 responses reflecting perceptual categorisation and motivational relevance respectively. The deletion group categorised food stimuli in terms of composition while the UPD group performed more similar to the controls, and focused on the suitability of food for consumption. Individual differences in N1 amplitude correlated with body mass index and scores on the Hyperphagia Questionnaire. Conclusion Differences are seen in how people with PWS because of deletion or UPD perceive visual food stimuli even within the first milliseconds of stimuli exposure. Implications are discussed for in vivo food behaviours and for future ERP or neuroimaging studies on hunger, satiety and food perception in PWS. [ABSTRACT FROM AUTHOR]

This study examined stress-support in 42 families of 3 to 18-year-old children with Prader-Willi syndrome. Parents were asked about themselves and their families, their child with Prader-Willi syndrome, family supports, and family stress. Compared to reported stress levels in families of children with mixed etiologies of retardation, parents of children with Prader-Willi syndrome showed higher levels of parent and family problems, and comparable levels of pessimism. Parents of children with Prader-Willi syndrome listed other family members and friends as their main supporters; often such supporters lived outside of the respondent's town or city. Although the child's age, IQ, and degree of obesity were not related to familial stress, families experienced greater stress when the child showed more behavior problems overall, more externalizing and internalizing problems, and more problems on five of the nine narrow-band domains of Achenbach's Child Behavior Checklist. [ABSTRACT FROM AUTHOR]

Background: Prader-Willi syndrome (PWS) is a rare, neurodevelopmental disorder caused by the lack of expression of paternally imprinted genes on chromosome 15q11-13. PWS features a complex behavioral phenotype, including hyperphagia, anxiety, compulsivity, rigidity, repetitive speech, temper outbursts, aggressivity, and skin-picking. Questionnaires exist for measuring hyperphagia, but not for the aggregation of other problems that are distinctive to PWS. A PWS-specific tool is needed for phenotypic research, and to help evaluate treatment efficacy in future clinical trials aimed at attenuating PWS's hyperphagia and related problems. In this 4-phase study, we leveraged our expertise in PWS with feedback from families and specialists to validate the PWS Profile, a novel, informant-based measure of behavioral and emotional problems in this syndrome., Results: The authors developed a bank of 73 items that tapped both common and less frequent but clinically significant problems in PWS (Phase 1). An iterative feedback process with families and stakeholders was used to ensure content and construct validity (Phase 2). After adding, omitting, or revising items, in Phase 3, we pilot tested the measure in 112 participants. Results were reviewed by an international team of PWS specialists and revised again (Phase 3). The final, 57-item Profile was then administered to 761 participants (Phase 4). Principal component factor analyses (n = 873) revealed eight conceptually meaningful factors, accounting for 60.52% of test variance, and were readily interpretated as: Rigidity, Insistence; Aggressive Behaviors; Repetitive Questioning, Speech; Compulsive Behaviors; Depression, Anxiety; Hoarding; Negative Distorted Thinking; and Magical Distorted Thinking. Factors were internally consistent and showed good test-retest reliability and convergent validity with existent measures of behavioral problems. Profile factors were not related to IQ, BMI, or parental SES. Three Profile factors differed across PWS genetic subtypes. Age and gender differences were found in only one Profile factor, Hoarding., Conclusions: The PWS Profile is a valid, psychometrically-sound questionnaire that already has shown responsivity to treatment in a previous clinical trial. The Profile can extend the reach of future clinical trials by evaluating the impact of novel agents not only on hyperphagia, but also on the emotional and behavioral problems that characterize PWS., (© 2024. The Author(s).)

This randomized controlled trial (NCT03889821) examined Mindfulness Based Stress Reduction (MBSR) in conjunction with the Parent-implemented Early Start Denver Model (P-ESDM). A previous report described improved metrics of parental distress (Weitlauf et al. in Pediatrics 145(Supplement 1):S81-S92, 2020). This manuscript examines child outcomes. 63 children with ASD (< 36 months) and their parents received 12 P-ESDM sessions. Half of parents also received MBSR. Longitudinal examination of whole sample means revealed modest improvements in autism severity, cognitive, and adaptive skills. There was not a significant time × group interaction for children whose parents received MBSR. Future work should examine more proximal markers of child or dyadic change to enhance understanding of the impact of providing direct treatment for parents as part of early intervention initiatives., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: People with neurodevelopmental disabilities, including Prader-Willi syndrome (PWS), are at heightened risk for the negative sequalae of loneliness, including depression and anxiety. While societal factors such as stigma or limited social opportunities contribute to loneliness, so too do deficits in social cognition and social skills. People with PWS have specific difficulties recognizing affect in others, accurately interpreting social interactions, and taking the perspectives of others. These features, combined with hyperphagia, rigidity, and insistence on sameness conspire to impede the abilities of people with PWS to make and sustain friendships and reduce feelings of loneliness., Methods: We developed and administered an intervention, Building Our Social Skills (BOSS), that aimed to improve social skill deficits in PWS. The 10-week intervention was administered on-line via Zoom to 51 young people with PWS in the U.S. (M age = 20.8, SD = 6.42). Two clinicians co-led groups of 6-8 participants in 30-min sessions, 3 times per week, and also trained 4 graduate students to co-lead groups with high fidelity. We used a pre-post intervention and 3-month follow-up design, with no control group, and mitigated this design limitation by triangulating across informants and methodologies. Specifically, parents completed the widely used Social Responsiveness Scale (SRS) and Child Behavior Checklist (CBCL), and participants were individually interviewed about their friendships and loneliness. Interview responses were reliably coded by independent raters., Results: Repeated measure multivariate analyses, with baseline values entered as covariates, revealed significant pre-to post-test improvements in the SRS's social cognition, motivation and communication subscales ( p 's < 0.001), with large effect sizes ( n p 2 = 0.920, 0.270, and 0.204, respectively). Participant and parental reports of loneliness were correlated with the CBCL's Internalizing domain, specifically the Anxiety/Depressed subdomain. Over time, parents reported getting along better with peers, increased contact with friends, more friends and less loneliness. Participants also reported significantly less loneliness and more friends., Conclusions: This mixed method, proof-of-concept study demonstrated the feasibility of delivering an on-line social skills intervention to young people with PWS. As no differences were found between clinician vs. graduate student outcomes, the BOSS curriculum holds considerable promise for wider dissemination and implementation in the PWS community., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dykens, Roof, Hunt-Hawkins and McDonald.)

Background: Despite work on the self-identities of people with intellectual disabilities, research has yet to describe the self-perceptions of people with Prader-Willi syndrome (PWS). The perspectives of those with PWS are also important for rapidly evolving clinical trials aimed at treating symptoms of PWS., Method: Twenty-one young people with PWS were administered a semi-structured interview that assessed how they perceive their syndrome and clinical trials. Transcribed interviews were reliably coded using content-driven, applied thematic analyses., Results: Five themes emerged: struggles with chronic hunger and food-seeking that impede goals and relationships; struggles with anxiety and outbursts, schedule changes and school; distancing from PWS; needs for clinical trials that cure PWS, reduce hunger or anxiety, and lead to improved outcomes; and needs for advocacy and awareness of PWS., Conclusions: Findings shed new light on the self-perceptions of those with PWS and have important implications for current interventions and future clinical trials., (© 2021 John Wiley & Sons Ltd.)

This study assessed 155 healthcare providers, from nine disciplines, who work professionally with people with intellectual and developmental disabilities (IDD). Using a national, web-based survey, respondents rated their experience, comfort, and competence in treating individuals with different disability types and preferred methods of continuing education; respondents also provided suggestions for attracting others to work with the IDD population. Findings revealed that experiences, comfort, and competence were all higher concerning persons with autism spectrum disorder (ASD) and intellectual disability (ID), lower for those with deaf-blindness. Overall, levels of experience exceeded levels of comfort, which in turn exceeded levels of competence. The most helpful venues for continued training involved day-to-day contact with persons with IDD, which also characterized open-ended responses. Research and practical implications are discussed., (©AAIDD.)

Background: Adequate sleep is important for proper neurodevelopment and positive health outcomes. Sleep disturbances are more prevalent in children with genetically determined neurodevelopmental syndromes compared with typically developing counterparts. We characterize sleep behavior in Rett (RTT), Angelman (AS), and Prader-Willi (PWS) syndromes to identify effective approaches for treating sleep problems in these populations. We compared sleep-related symptoms across individuals with these different syndromes with each other, and with typically developing controls., Methods: Children were recruited from the Rare Diseases Clinical Research Network consortium registries; unaffected siblings were enrolled as related controls. For each participant, a parent completed multiple sleep questionnaires including Pediatric Sleep Questionnaire (Sleep-Disordered Breathing), Children's Sleep Habits Questionnaire (CSHQ), and Pediatric Daytime Sleepiness Scale., Results: Sleep data were analyzed from 714 participants, aged two to 18 years. Young children with AS had more reported sleep problems than children with RTT or PWS. Older children with RTT had more reported daytime sleepiness than those with AS or PWS. Finally, all individuals with RTT had more evidence of sleep-disordered breathing when compared with individuals with PWS. Notably, typically developing siblings were also reported to have sleep problems, except for sleep-related breathing disturbances, which were associated with each of the genetic syndromes., Conclusions: Individuals with RTT, AS, and PWS frequently experience sleep problems, including sleep-disordered breathing. Screening for sleep problems in individuals with these and other neurogenetic disorders should be included in clinical assessment and managements. These data may also be useful in developing treatment strategies and in clinical trials., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background and Objectives: Systems of care emphasize parent-delivered intervention for children with autism spectrum disorder (ASD). Meanwhile, multiple studies document psychological distress within these parents. This pilot longitudinal randomized controlled trial compared the parent-implemented Early Start Denver Model (P-ESDM) to P-ESDM plus mindfulness-based stress reduction (MBSR) for parents. We evaluated changes in parent functioning during active treatment and at follow-up., Methods: Participants included children (<36 months old) with autism spectrum disorder and caregivers. Participants were randomly assigned to P-ESDM only ( n = 31) or P-ESDM plus MBSR ( n = 30). Data were collected at baseline, midtreatment, the end of treatment, and 1, 3, and 6 months posttreatment. Multilevel models with discontinuous slopes were used to test for group differences in outcome changes over time., Results: Both groups improved during active treatment in all subdomains of parent stress (β = -1.42, -1.25, -0.92; P < 0.001), depressive symptoms, and anxiety symptoms (β = -0.62 and -0.78, respectively; P < 0.05). Parents who received MBSR had greater improvements than those receiving P-ESDM only in parental distress and parent-child dysfunctional interactions (β = -1.91 and -1.38, respectively; P < 0.01). Groups differed in change in mindfulness during treatment (β = 3.15; P < .05), with P-ESDM plus MBSR increasing and P-ESDM declining. Treatment group did not significantly predict change in depressive symptoms, anxiety symptoms, or life satisfaction. Differences emerged on the basis of parent sex, child age, and child behavior problems., Conclusions: Results suggest that manualized, low-intensity stress-reduction strategies may have long-term impacts on parent stress. Limitations and future directions are described., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

Introduction: People with Prader-Willi syndrome (PWS) have a distinctive behavioral phenotype that includes intellectual disability, compulsivity, inattention, inflexibility and insistence on sameness. Inflexibility and inattention are at odds with the cognitive flexibility and attention to social cues needed to accurately perceive the social world, and implicate problems in social cognition. This study assessed two social cognition domains in people with PWS; emotion recognition and social perception. We identified changes in social cognition over an approximate two-year time period (M = 2.23 years), relative strengths and weakness in social cognition, and correlates and predictors of social cognition., Methods: Emotion recognition and social perception were examined at two time points in 94 individuals with PWS aged 5 to 62 years (M = 13.81, SD = 10.69). Tasks administered included: standardized IQ testing; parent-completed measures of inattention and inflexibility; standard emotion recognition photos (fear, sadness, anger, happy); and videotaped social perception vignettes depicting negative events with either sincere/benign or insincere/hostile interactions between peers., Results: An atypical trajectory of negative emotion recognition emerged, marked by similar levels of poor performances across age, and confusion between sad and anger that is typically resolved in early childhood. Recognition of sad and fear were positively correlated with IQ. Participants made gains over time detecting social cues, but not in forming correct conclusions about the intentions of others. Accurately judging sincere intentions remained a significant weakness over time. Relative to sincere intentions, participant's performed significantly better in detecting negative social cues, and correctly judging trickery, deceit and lying. Age, IQ, inattention, and recognition of happy and sad accounted for 29% of variance in social perception., Conclusion: Many people with PWS have deficits in recognizing sad, anger and fear, and accurately perceiving the sincere intentions of other people. The impact of these deficits on social behavior and relationships need to be better understood., Competing Interests: The authors have declared that no competing interests exist.

Background: Prader-Willi syndrome (PWS) is a genetic neurodevelopmental disorder of life-threatening hyperphagia, obesity, intellectual deficits, compulsivity, and other behavioral problems. The efficacy and safety of i.n. carbetocin, an oxytocin analog, was evaluated in a prospective, randomized, double-blinded trial in adolescents with PWS., Methods: Eligible patients aged 10-18 years with genetically confirmed PWS were randomized (1:1) to i.n. carbetocin or placebo 3 times daily for 14 days. The primary efficacy endpoint was change in parent/caregiver-rated Hyperphagia in PWS Questionnaire-Responsiveness (HPWSQ-R) total score. Secondary efficacy endpoints included HPWSQ-R behavior, drive, and severity domains; clinician-rated HPWSQ; Children's Yale-Brown Obsessive-Compulsive Severity Scale; food domain of the Reiss Profile; and Clinical Global Impression-Improvement scale. Endpoints were assessed using analysis of covariance. Relationship between primary and secondary endpoints was assessed using Pearson correlation coefficients. Safety was assessed throughout the study., Results: Demographics and clinical characteristics were similar between treatment groups (carbetocin, n = 17; placebo, n = 20). Patients receiving carbetocin had statistically significant reductions in HPWSQ-R total score at study end (-15.6) versus patients receiving placebo (-8.9; P = 0.029); several secondary efficacy endpoints also demonstrated significant differences (P < 0.05). Treatment effects for the primary and secondary endpoints were highly correlated (P ≤ 0.0001). Incidence of adverse events (AEs) was similar between treatment groups., Conclusion: I.n. carbetocin was well tolerated and improved hyperphagia and behavioral symptoms of PWS., Trial Registration: ClinicalTrials.gov: NCT01968187FUNDING. The study was funded by Ferring Pharmaceuticals. Recruitment was aided by ongoing work in PWS performed through Eunice Kennedy Shriver National Institute of Child Health and Human Development grant U54 HD083211.

Individuals with Williams Syndrome (WS) exhibit an atypical auditory profile. Across two experiments, we used event-related potentials (ERPs) in a three-stimulus auditory oddball task to examine early sensory (P1, N1, P2) and later cognitive (P3a, P3b) stages of cortical auditory processing in adults with WS and age-matched typical peers. In Study 1, piano chords served as standard, target, and novel stimuli; whereas, in Study 2, a variety of non-piano sounds comprised the novel stimuli. Across both experiments, there were no group differences in the earliest stages of sensory encoding (P1, N1), along with evidence for atypically large P2 responses in participants with WS. Persons with WS exhibited larger than typical P3a responses when the novel stimuli were perceptually distinct from the standard and the target stimuli (Study 2), but not when task-relevant and -irrelevant stimuli were perceptually similar (Study 1). Further, the WS group demonstrated reduced goal-directed attention (attenuated P3b response). These group differences in ERPs were not directly related to IQ. Our results in the context of an active discrimination task point to a more complex profile of auditory processing in persons with WS than previously reported, with group differences emerging during the later stages of stimulus categorization and evaluation, but not within early stimulus detection and feature encoding., (Copyright © 2018 Elsevier Inc. All rights reserved.)

This study examined the feasibility of eye tracking measures as markers of hyperphagia in 42 children and adults with Prader-Willi syndrome (PWS). Gaze data collected during free visual exploration of complex displays revealed that food images may not have an overall superior salience in PWS. However, increased attention to food in the context of other high-interest items was associated with higher scores on caregiver reports of hyperphagia. The study also provided preliminary evidence of test-retest reliability of eye tracking measures, suggesting that gaze characteristics may be a promising objective marker of food-related interests in PWS.

Aims: There are no treatments for the extreme hyperphagia and obesity in Prader-Willi syndrome (PWS). The bestPWS clinical trial assessed the efficacy, safety and tolerability of the methionine aminopeptidase 2 (MetAP2) inhibitor, beloranib., Materials and Methods: Participants with PWS (12-65 years old) were randomly assigned (1:1:1) to biweekly placebo, 1.8 mg beloranib or 2.4 mg beloranib injection for 26 weeks at 15 US sites. Co-primary endpoints were the changes in hyperphagia [measured by Hyperphagia Questionnaire for Clinical Trials (HQ-CT); possible score 0-36] and weight by intention-to-treat. ClinicalTrials.gov registration: NCT02179151., Results: One-hundred and seven participants were included in the intention-to-treat analysis: placebo (n = 34); 1.8 mg beloranib (n = 36); or 2.4 mg beloranib (n = 37). Improvement (reduction) in HQ-CT total score was greater in the 1.8 mg (mean difference -6.3, 95% CI -9.6 to -3.0; P = .0003) and 2.4 mg beloranib groups (-7.0, 95% CI -10.5 to -3.6; P = .0001) vs placebo. Compared with placebo, weight change was greater with 1.8 mg (mean difference - 8.2%, 95% CI -10.8 to -5.6; P < .0001) and 2.4 mg beloranib (-9.5%, 95% CI -12.1 to -6.8; P < .0001). Injection site bruising was the most frequent adverse event with beloranib. Dosing was stopped early due to an imbalance in venous thrombotic events in beloranib-treated participants (2 fatal events of pulmonary embolism and 2 events of deep vein thrombosis) compared with placebo., Conclusions: MetAP2 inhibition with beloranib produced statistically significant and clinically meaningful improvements in hyperphagia-related behaviours and weight loss in participants with PWS. Although investigation of beloranib has ceased, inhibition of MetAP2 is a novel mechanism for treating hyperphagia and obesity., (© 2017 John Wiley & Sons Ltd.)

Background: A small percentage of people with autism spectrum disorders (ASD) have alterations in chromosome 15q11.2-q3, the critical region for Prader-Willi syndrome (PWS). Data are limited, however, on the rates and characteristics of ASD in PWS. Previous estimates of ASD in PWS (25 to 41%) are questionable as they are based solely on autism screeners given to parents. Inaccurate diagnoses of ASD in PWS can mislead intervention and future research., Methods: One hundred forty-six children and youth with PWS aged 4 to 21 years ( M  = 11) were assessed with the Autism Diagnostic Observation Schedule-2 (ADOS-2). An expert clinical team-made best-estimate ASD diagnoses based on ADOS-2 videotapes, calibrated severity scores, and children's developmental histories and indices of current functioning. Children were also administered the Kaufman Brief Intelligence Test-2, and parents completed the Repetitive Behavior Scale-Revised and Vineland Adaptive Behavior Scales. Scores were compared across children with PWS + ASD versus PWS only. The performance of an ASD screener, the Social Communication Questionnaire (SCQ) and the ADOS-2 were evaluated in relation to best-estimate diagnoses., Results: Best-estimate diagnoses of ASD were made in 18 children, or 12.3% of the sample, and the majority of them had the maternal uniparental disomy (mUPD) PWS genetic subtype. Compared to the PWS-only group, children with PWS + ASD had lower verbal and composite IQ's and adaptive daily living and socialization skills, as well as elevated stereotypies and restricted interests. Regardless of ASD status, compulsivity and insistence on sameness in routines or events were seen in 76-100% of children and were robustly correlated with lower adaptive functioning. The SCQ yielded a 29-49% chance that screen-positive cases will indeed have ASD. The ADOS-2 had higher sensitivity, specificity and predictive values. Communication problems were seen in children who were ADOS-2 positive but deemed not to have ASD by the clinical team., Conclusions: Autism screeners should not be the sole index of probable ASD in PWS; children need to be directly observed and evaluated. Compulsivity and insistence on sameness are salient in PWS and likely impede adaptive functioning. Most children with PWS only evidenced sub-threshold problems in social interactions that could signal risks for other psychopathologies.

The present study examined the effects of genetic subtype on social memory in children (7-16 years) with Prader-Willi syndrome (PWS). Visual event-related potentials (ERPs) during a passive viewing task were used to compare incidental memory traces for repeated vs single presentations of previously unfamiliar social (faces) and nonsocial (houses) images in 15 children with the deletion subtype and 13 children with maternal uniparental disomy (mUPD). While all participants perceived faces as different from houses (N170 responses), repeated faces elicited more positive ERP amplitudes ('old/new' effect, 250-500ms) only in children with the deletion subtype. Conversely, the mUPD group demonstrated reduced amplitudes suggestive of habituation to the repeated faces. ERP responses to repeated vs single house images did not differ in either group. The results suggest that faces hold different motivational value for individuals with the deletion vs mUPD subtype of PWS and could contribute to the explanation of subtype differences in the psychiatric symptoms, including autism symptomatology., (© The Author (2017). Published by Oxford University Press.)

Siblings of brothers or sisters with intellectual and developmental disabilities (IDD) are important but understudied family members. As many previous studies have relied on parent report of sibling outcomes, the use of sibling self-report is an important addition to the research. This study assessed the feelings of adolescent siblings toward their brothers or sisters with and without IDD, as well as broader aspects of sibling empathy. Data were collected via a national, online survey from 97 parent-sibling pairs. Siblings of individuals with IDD reported higher levels of anxiety toward the target child than did siblings of typically developing individuals. Sibling feelings toward the target child were related to both parental and target child factors, but only among families of individuals with IDD.

Background: People with Prader-Willi syndrome (PWS) typically have mild to moderate intellectual deficits, compulsivity, hyperphagia, obesity, and growth hormone deficiencies. Growth hormone treatment (GHT) in PWS has well-established salutatory effects on linear growth and body composition, yet cognitive benefits of GHT, seen in other patient groups, have not been well studied in PWS., Methods: Study 1 included 96 children and youth with PWS aged 4-21 years who naturalistically varied in their exposures to GHT. Controlling for socioeconomic status, analyses compared cognitive and adaptive behavior test scores across age-matched treatment naïve versus growth hormone treated children. Study II assessed if age of treatment initiation or treatment duration was associated with subsequent cognition or adaptive behavior in 127, 4- to 21-year olds with PWS. Study III longitudinally examined cognitive and adaptive behavior in 168 participants who were either consistently on versus off GHT for up to 4-5 years., Results: Compared to the treatment naïve group, children receiving GHT had significantly higher Verbal and Composite IQs, and adaptive communication and daily living skills. Children who began treatment before 12 months of age had higher Nonverbal and Composite IQs than children who began treatment between 1 and 5 years of age. Longitudinally, the groups differed in their intercepts, but not slopes, with each group showing stable IQ and adaptive behavior scores over time., Conclusions: Cognitive and adaptive advantages should be considered an ancillary benefit and additional justification for GHT in people with PWS. Future efforts need to target apparent socioeconomic inequities in accessing GHT in the PWS population., Competing Interests: No conflicts declared., (© 2016 Association for Child and Adolescent Mental Health.)

The present study examined possible neural mechanisms underlying increased social interest in persons with Williams syndrome (WS). Visual event-related potentials (ERPs) during passive viewing were used to compare incidental memory traces for repeated vs. single presentations of previously unfamiliar social (faces) and nonsocial (houses) images in 26 adults with WS and 26 typical adults. Results indicated that participants with WS developed familiarity with the repeated faces and houses (frontal N400 response), but only typical adults evidenced the parietal old/new effect (previously associated with stimulus recollection) for the repeated faces. There was also no evidence of exceptional salience of social information in WS, as ERP markers of memory for repeated faces vs. houses were not significantly different. Thus, while persons with WS exhibit behavioral evidence of increased social interest, their processing of social information in the absence of specific instructions may be relatively superficial. The ERP evidence of face repetition detection in WS was independent of IQ and the earlier perceptual differentiation of social vs. nonsocial stimuli. Large individual differences in ERPs of participants with WS may provide valuable information for understanding the WS phenotype and have relevance for educational and treatment purposes.

Background: Williams syndrome (WS) is associated with a distinct cognitive-behavioural phenotype including mild to moderate intellectual disability, visual-spatial deficits, hypersociability, inattention and anxiety. Researchers typically characterise samples of individuals with WS by their intellectual functioning and adaptive behaviour. Because of the low prevalence of the syndrome, researchers often include participants with WS across a broad age range throughout childhood and adulthood and assume participants demonstrate consistent cognitive development across ages. Indeed, IQ scores are generally stable for children and adolescents with WS, although there are significant individual differences. It is less clear whether this pattern of stable intellectual ability persists into adulthood. Furthermore, while adaptive behaviour is an important indicator of an individual's ability to apply their conceptual skills to everyday functioning, conflicting findings on the trajectories of adaptive behaviour in adolescents and adults with WS have been reported. The current study examined longitudinal profiles of cognitive and adaptive functioning in adolescents and adults with WS., Method: To examine cognitive functioning, participants included 52 individuals with WS (51.9% men) who were assessed with the Kaufman Brief Intelligence Test, 2nd edition (KBIT-2) between two and seven times. At their first assessment, participants had a mean age of 25.4 years (SD = 8.4), ranging in age from 14.2 to 48.9 years. To assess adaptive behaviour, participants included a subset of 28 individuals with WS whose parents completed the Vineland Adaptive Behavior Scale, 2nd edition (VABS-II) between two and five times. At their initial administration, participants ranged from 17.1-40.2 years of age, with a mean age of 26.5 years (SD = 7.3). A series of multilevel models were used to examine changes in KBIT-2 Composite IQ, Verbal IQ and Nonverbal IQ standard scores over time, as well as the Adaptive Behavior Composite, and the Communication, Daily Living Skills and Socialization subdomains of the VABS-II., Results: Consistent with the WS cognitive profile, IQ scores were significantly lower than the general population IQ score of 100, and there was significant variability in individual IQ scores and slopes. KBIT-2 IQ scores were generally stable across adolescents and adults with WS. Adaptive behaviour scores were significantly lower than the population mean score of 100, and there was significant variability in individuals' adaptive behaviour scores but not trajectories. However, in contrast to the findings with the KBIT-2, VABS-II scores were observed to significantly decrease over time., Conclusion: Findings suggest that while intellectual functioning remains stable, adaptive functioning does not remain stable across adolescence and adulthood in individuals with WS. Implications for the relation between cognitive and adaptive functioning across development are discussed, with a focus on how this relates to specific aspects of the WS phenotype., (© 2016 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.)

Background: Individuals with Williams syndrome (WS) exhibit hypersociability and may respond atypically to emotional information in social and nonsocial stimuli. It is not yet clear whether these difficulties are specific to emotional content or stimulus type. This study examined the neural processes supporting social and emotional information processing in WS., Method: Visual event-related potentials were recorded in 19 adults with WS and 10 typical peers during a picture-viewing task requiring detection of smiling faces among other social and nonsocial images with positive and negative emotional content., Results: The participant groups were not significantly different in affective processing of positive and negative stimuli and perceived faces as different from nonsocial images. Participants with WS showed subtle differences in face-specific perceptual processes (e.g. face inversion, N170 lateralisation), suggesting a more feature-based processing. They also demonstrated reduced attention and arousal modulation (P3, late positive potential) in response to faces vs. nonsocial images. These differences were independent of intelligence quotient., Conclusions: There was no evidence of greater than typical perceptual, attentional or affective processing of social information in WS. The results support the idea that altered face perception processes and not the increased salience of social stimuli or difficulties with emotion discrimination may contribute to the hypersocial phenotype in WS., (© 2016 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.)

Beat perception in music has been proposed to be a human universal that may have its origins in adaptive processes involving temporal entrainment such as social communication and interaction. We examined beat perception skills in individuals with Williams syndrome (WS), a genetic, neurodevelopmental disorder. Musical interest and hypersociability are two prominent aspects of the WS phenotype although actual musical and social skills are variable. On a group level, beat and meter perception skills were poorer in WS than in age-matched peers though there was significant individual variability. Cognitive ability, sound processing style, and musical training predicted beat and meter perception performance in WS. Moreover, we found significant relationships between beat and meter perception and adaptive communication and socialization skills in WS. Results have implications for understanding the role of predictive timing in both music and social interactions in the general population, and suggest music as a promising avenue for addressing social communication difficulties in WS.

Mothers of individuals with Prader-Willi syndrome (PWS) often experience numerous stressors, even when compared to mothers of children with other intellectual and developmental disabilities. Despite this, these mothers show great variability in self-reported life satisfaction. Using data from a longitudinal study of individuals with PWS and their families, the present study analyzed factors related to maternal life satisfaction, both cross-sectionally and over time. Results show that both child factors (e.g., behavior problems, hyperphagia) and maternal factors (e.g., stress, coping style) were significantly related to maternal life satisfaction. However, none of the tested variables predicted change in life satisfaction over time. Research and practice implications are discussed.

The emergence of resting-state functional connectivity (rsFC) analysis, which examines temporal correlations of low-frequency (<0.1 Hz) blood oxygen level-dependent signal fluctuations between brain regions, has dramatically improved our understanding of the functional architecture of the typically developing (TD) human brain. This study examined rsFC in Down syndrome (DS) compared with another neurodevelopmental disorder, Williams syndrome (WS), and TD. Ten subjects with DS, 18 subjects with WS, and 40 subjects with TD each participated in a 3-Tesla MRI scan. We tested for group differences (DS vs. TD, DS vs. WS, and WS vs. TD) in between- and within-network rsFC connectivity for seven functional networks. For the DS group, we also examined associations between rsFC and other cognitive and genetic risk factors. In DS compared with TD, we observed higher levels of between-network connectivity in 6 out 21 network pairs but no differences in within-network connectivity. Participants with WS showed lower levels of within-network connectivity and no significant differences in between-network connectivity relative to DS. Finally, our comparison between WS and TD controls revealed lower within-network connectivity in multiple networks and higher between-network connectivity in one network pair relative to TD controls. While preliminary due to modest sample sizes, our findings suggest a global difference in between-network connectivity in individuals with neurodevelopmental disorders compared with controls and that such a difference is exacerbated across many brain regions in DS. However, this alteration in DS does not appear to extend to within-network connections, and therefore, the altered between-network connectivity must be interpreted within the framework of an intact intra-network pattern of activity. In contrast, WS shows markedly lower levels of within-network connectivity in the default mode network and somatomotor network relative to controls. These findings warrant further investigation using a task-based procedure that may help disentangle the relationship between brain function and cognitive performance across the spectrum of neurodevelopmental disorders.

Purpose of Review: Developmental disabilities are increasingly recognized, and remarkable progress is being made on the genetic and neurobiological underpinnings of many disorders. Yet, only a tiny percentage of the disability literature addresses families of children with disabilities. A review of recently published family studies reveals salient trends and gaps., Recent Findings: Consistent with previous work, high levels of parent stress, illness, anxiety, and depression are apparent. Studies in the USA focused on parents of children with autism; in contrast, studies on parents of children with intellectual disabilities were almost always conduced abroad. Compared to other disabilities, families of children with psychiatric disorders and genetic syndromes are understudied. The majority of family studies are descriptive, with very few trials or interventions aimed at reducing parental stress. Of these, mindfulness practices and a peer-mentor model of treatment delivery hold much promise for effective stress reduction. Psychoeducational programs and respite care are differentially beneficial., Summary: A new era of family intervention research is in order. This work can take advantage of many advances in telemedicine, peer-mentor models, smart technology, and biomarkers as indices of change. Benefit could also stem from group interventions with parents who share similar concerns, regardless of their child's diagnostic label.

Background: Relative to other aspects of Down syndrome, remarkably little is known about the psychiatric problems experienced by youth and young adults with this syndrome and if these problems differ from others with intellectual disabilities. Yet adolescence and young adulthood are particularly vulnerable time periods, as they involve multiple life transitions in educational, medical, and other service systems., Methods: This study compared the psychiatric diagnoses of 49 adolescent and young adult patients with Down syndrome to 70 patients with other intellectual disabilities (IDs). The groups were similar in age, gender, and level of intellectual impairment. The 119 participants, aged 13 to 29 years (M = 21) were evaluated in one of two specialized psychiatric clinics., Results: In contrast to previous literature, those with Down syndrome versus other IDs had significantly higher rates of psychosis NOS or depression with psychotic features (43% versus 13%). Unlike the ID group, psychosis was predominantly seen in females with Down syndrome. Marked motoric slowing in performing routine daily activities or in expressive language was manifested in 17% of patients with Down syndrome. No group differences were found in anxiety or depressive disorders, and the ID group had significantly higher rates of bipolar and impulse control disorders., Conclusions: These preliminary observations warrant further studies on genetic, neurological, and psychosocial factors that place some young people with Down syndrome or other IDs at high risk for severe psychiatric illness.

Given the reliance on self-report in studies of adults with intellectual disabilities, this study examined individual vs. parental reports concerning the social approach behaviors of adults with Williams syndrome (WS) across a hypothetical and a live behavioral setting. Individuals with WS (N = 30) were asked whether they would approach strangers in two hypothetical, laboratory tasks (yes/no questionnaire vs. judging facial stimuli of individuals with different emotional expressions). Similarly, their parents also responded to a rating scale of their child's social approach behavior toward strangers displaying various emotions. Then, in a community setting, behavioral coders recorded actual social approaches of individuals with WS toward strangers. Although self-report ratings were consistent across measures, these measures did not correspond to the individuals' actual behaviors during the community observations. Conversely, parental reports did not correspond to their child's self-report measures, but parents did more accurately predict their child's real-life social approach behaviors. Implications are discussed for both research and practice., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Congenital amusia is defined by marked deficits in pitch perception and production. Though historically examined only in otherwise typically developing (TD) populations, amusia has recently been documented in Williams syndrome (WS), a genetic, neurodevelopmental disorder with a unique auditory phenotype including auditory sensitivities and increased emotional responsiveness to music but variable musical skill. The current study used structural T1-weighted magnetic resonance imaging and diffusion tensor imaging to examine neural correlates of amusia in 17 individuals with WS (4 of whom met criteria for amusia). Consistent with findings from TD amusics, amusia in WS was associated with decreased fractional anisotropy (FA) in the right superior longitudinal fasciculus (SLF). The relationship between amusia and FA in the inferior component of the SLF was particularly robust, withstanding corrections for cognitive functioning, auditory sensitivities, or musical training. Though the number of individuals with amusia in the study is small, results add to evidence for the role of fronto-temporal disconnectivity in congenital amusia and suggest that novel populations with developmental differences can provide a window into understanding gene-brain-behavior relationships that underlie musical behaviors.

Background: Compared with other parents, mothers of children with autism spectrum disorder or other neurodevelopmental disabilities experience more stress, illness, and psychiatric problems. Although the cumulative stress and disease burden of these mothers is exceptionally high, and associated with poorer outcomes in children, policies and practices primarily serve the identified child with disabilities., Methods: A total of 243 mothers of children with disabilities were consented and randomized into either Mindfulness-Based Stress Reduction (mindfulness practice) or Positive Adult Development (positive psychology practice). Well-trained, supervised peer mentors led 6 weeks of group treatments in 1.5-hour weekly sessions, assessing mothers 6 times before, during, and up to 6 months after treatment. Mothers had children with autism (65%) or other disabilities (35%). At baseline, 85% of this community sample had significantly elevated stress, 48% were clinically depressed, and 41% had anxiety disorders., Results: Using slopes-as-outcomes, mixed random effects models, both treatments led to significant reductions in stress, depression, and anxiety, and improved sleep and life satisfaction, with large effects in depression and anxiety. Mothers in Mindfulness-Based Stress Reduction versus Positive Adult Development had greater improvements in anxiety, depression, sleep, and well-being. Mothers of children with autism spectrum disorder improved less in anxiety, but did not otherwise differ from their counterparts., Conclusions: Future studies are warranted on how trained mentors and professionals can address the unmet mental health needs of mothers of children with developmental disabilities. Doing so improves maternal well-being and furthers their long-term caregiving of children with complex developmental, physical, and behavioral needs., (Copyright © 2014 by the American Academy of Pediatrics.)

Emotional connection is the main reason people engage with music, and the emotional features of music can influence processing in other domains. Williams syndrome (WS) is a neurodevelopmental genetic disorder where musicality and sociability are prominent aspects of the phenotype. This study examined oscillatory brain activity during a musical affective priming paradigm. Participants with WS and age-matched typically developing controls heard brief emotional musical excerpts or emotionally neutral sounds and then reported the emotional valence (happy/sad) of subsequently presented faces. Participants with WS demonstrated greater evoked fronto-central alpha activity to the happy vs sad musical excerpts. The size of these alpha effects correlated with parent-reported emotional reactivity to music. Although participant groups did not differ in accuracy of identifying facial emotions, reaction time data revealed a music priming effect only in persons with WS, who responded faster when the face matched the emotional valence of the preceding musical excerpt vs when the valence differed. Matching emotional valence was also associated with greater evoked gamma activity thought to reflect cross-modal integration. This effect was not present in controls. The results suggest a specific connection between music and socioemotional processing and have implications for clinical and educational approaches for WS.

Although hyperphagia and compulsivity in Prader-Willi syndrome (PWS) are well described, recreation and adaptive skills are relatively unexplored. Parents of 123 participants with PWS (4-48 years) completed measures of their child's adaptive, recreation, and problem behaviors. Offspring received cognitive testing. Watching TV was the most frequent recreational activity, and was associated with compulsivity and skin picking. BMIs were negatively correlated with physical play, and highest in those who watched TV and played computer games. Computer games and physical activities were associated with higher IQ and adaptive scores. People with PWS and other disabilities need to watch less TV and be more engaged in physical activities, games, and leisure pursuits that are fun, and may bring cognitive or adaptive advantages.

A major goal of aging research is to identify early markers of age-related cognitive decline. Persons with Down syndrome (DS) experience accelerated aging and high risks for dementia, making them a valuable albeit understudied model for testing such markers. This study examined event-related potential (ERP) indices of visual memory in younger (19-25 years) and older (35-40 years) adults with DS using a passive viewing paradigm that did not require memorization or behavioral responses. ERPs were recorded in response to unfamiliar urban and nature scenes, with some images presented once and others repeated multiple times. Within 600 to 900 milliseconds after stimulus onset, repeated stimuli elicited more positive amplitudes in younger participants, indicating stimilus recognition. ERPs of older adults did not show such increases, suggesting reduced memory functioning. ERP indices were unrelated to participants' intellectual functioning, but did correlate with age and caregiver-reported lethargy/withdrawal behaviors. Passive ERP measures of memory processes are sensitive to early stages of cognitive decline in DS and are promising markers of cognitive risk for future aging studies., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Individuals with Down Syndrome (DS) are reported to experience early onset of brain aging. However, it is not well understood how pre-existing neurodevelopmental effects versus neurodegenerative processes might be contributing to the observed pattern of brain atrophy in younger adults with DS. The aims of the current study were to: (1) to confirm previous findings of age-related changes in DS compared to adults with typical development (TD), (2) to test for an effect of these age-related changes in a second neurodevelopmental disorder, Williams syndrome (WS), and (3) to identify a pattern of regional age-related effects that are unique to DS., Methods: High-resolution T1-weighted MRI of the brains of subjects with DS, WS, and TD controls were segmented, and estimates of regional brain volume were derived using FreeSurfer. A general linear model was employed to test for age-related effects on volume between groups. Secondary analyses in the DS group explored the relationship between brain volume and neuropsychological tests and APOE., Results: Consistent with previous findings, the DS group showed significantly greater age-related effects relative to TD controls in total gray matter and in regions of the orbitofrontal cortex and the parietal cortex. Individuals with DS also showed significantly greater age-related effects on volume of the left and right inferior lateral ventricles (LILV and RILV, respectively). There were no significant differences in age-related effects on volume when comparing the WS and TD groups. In the DS group, cognitive tests scores measuring signs of dementia and APOE ϵ4 carrier status were associated with LILV and RILV volume., Conclusions: Individuals with DS demonstrated a unique pattern of age-related effects on gray matter and ventricular volume, the latter of which was associated with dementia rating scores in the DS group. Results may indicate that early onset of brain aging in DS is primarily due to DS-specific neurodegenerative processes, as opposed to general atypical neurodevelopment.

Prader-Willi syndrome (PWS) is one of the most commonly recognized causes of early-onset childhood obesity. Individuals with PWS have significant hyperphagia and decreased recognition of satiety. The exact etiology of the hyperphagia remains unknown and, therefore, untreatable. We conducted a pilot, open-label study of response to metformin in 21 children with PWS and six with early morbid obesity (EMO). Participants had significant insulin resistance and glucose intolerance on oral glucose tolerance testing (OGTT) and were started on metformin for these biochemical findings. We administered the Hyperphagia Questionnaire to parents of patients before and after starting metformin treatment. Both the PWS and EMO groups showed significant improvements in food-related distress, anxiety, and ability to be redirected away from food on the Hyperphagia Questionnaire. In the PWS group, improvements were predominantly seen in females. Within the PWS group, responders to metformin had higher 2-h glucose levels on OGTT (7.48 mmol/L vs. 4.235 mmol/L; p=0.003) and higher fasting insulin levels (116 pmol/L vs. 53.5 pmol/L; p=0.04). Additionally, parents of 5/13 individuals with PWS and 5/6 with EMO reported that their child was able to feel full while on metformin (for many this was the first time they had ever described a feeling of fullness). Metformin may improve sense of satiety and decrease anxiety about food in some individuals with PWS and EMO. Positive response to metformin may depend on the degree of hyperinsulinism and glucose intolerance. Nonetheless, the results of this pilot study bear further investigation.

This study used a stress biomarker, diurnal cortisol, to identify how elevated stress in mothers of children and adults with autism and other disabilities relates to their health and mental health. Based on semi-parametric, group-based trajectory analysis of 91 mothers, two distinctive cortisol trajectories emerged: blunted (63 %) or steep (37 %). Mothers in the blunted (vs. steep) trajectory had higher stress levels, lower health ratings, and 89 % of mothers of children with autism, and 53 % with other disabilities, belonged to this trajectory. Atypical cortisol awakening responses and evening rises were differentially associated with anxiety, depression, health problems and employment status. Stress-reducing interventions are needed for parents of children with autism and other disabilities that include biomarkers as indices of risk or treatment outcome.

Williams syndrome (WS) is a neurodevelopmental disorder associated with hypersociability and anxiety. However, little is known about how these salient aspects of the phenotype are related or their underlying physiology. We examined cortisol reactivity in WS because cortisol is responsive to psychosocial stress. Compared to typically developing adults, adults with WS had a significant cortisol decrease in response to a challenging cognitive battery. In contrast, cortisol levels in WS stayed stable in response to a solo musical performance, and baseline cortisol levels were significantly associated with musical skill. Results indicate that people with WS respond differentially to different socially-loaded situations. Implications for salience and arousal in cognitive and social situations are discussed.

Williams syndrome (WS), a genetic, neurodevelopmental disorder, is of keen interest to music cognition researchers because of its characteristic auditory sensitivities and emotional responsiveness to music. However, actual musical perception and production abilities are more variable. We examined musicality in WS through the lens of amusia and explored how their musical perception abilities related to their auditory sensitivities, musical production skills, and emotional responsiveness to music. In our sample of 73 adolescents and adults with WS, 11% met criteria for amusia, which is higher than the 4% prevalence rate reported in the typically developing (TD) population. Amusia was not related to auditory sensitivities but was related to musical training. Performance on the amusia measure strongly predicted musical skill but not emotional responsiveness to music, which was better predicted by general auditory sensitivities. This study represents the first time amusia has been examined in a population with a known neurodevelopmental genetic disorder with a range of cognitive abilities. Results have implications for the relationships across different levels of auditory processing, musical skill development, and emotional responsiveness to music, as well as the understanding of gene-brain-behavior relationships in individuals with WS and TD individuals with and without amusia.

Williams syndrome (WS) is a neurodevelopmental genetic disorder associated with high rates of anxiety and social issues. We examined diurnal cortisol, a biomarker of the stress response, in adults with WS in novel and familiar settings, and compared these profiles to typically developing (TD) adults. WS and TD participants had similar profiles in a familiar setting, while participants with WS had elevated cortisol late in the day in the novel setting when social demands were higher. The cortisol awakening response in WS was associated with parent-reported levels of somatic complaints and social difficulties. Results suggest that adults with WS have a typical diurnal cortisol profile that may be sensitive to social and activity transitions throughout the day.

Background: People with Prader-Willi syndrome (PWS) demonstrate social dysfunction and increased risk of autism spectrum disorder, especially those with the maternal uniparental disomy (mUPD) versus paternal deletion genetic subtype. This study compared the neural processing of social (faces) and nonsocial stimuli, varying in emotional valence, across genetic subtypes in 24 adolescents and adults with PWS., Methods: Upright and inverted faces, and nonsocial objects with positive and negative emotional valence were presented to participants with PWS in an oddball paradigm with smiling faces serving as targets. Behavioral and event-related potential (ERP) data were recorded., Results: There were no genetic subtype group differences in accuracy, and all participants performed above chance level. ERP responses revealed genetic subtype differences in face versus object processing. In those with deletions, the face-specific posterior N170 response varied in size for face stimuli versus inverted faces versus nonsocial objects. Persons with mUPD generated N170 of smaller amplitude and showed no stimulus differentiation. Brain responses to emotional content did not vary by subtype. All participants elicited larger posterior and anterior late positive potential responses to positive objects than to negative objects. Emotion-related differences in response to faces were limited to inverted faces only in the form of larger anterior late positive potential amplitudes to negative emotions over the right hemisphere. Detection of the target smiling faces was evident in the increased amplitude of the frontal and central P3 responses but only for inverted smiling faces., Conclusion: Persons with the mUPD subtype of PWS may show atypical face versus object processes, yet both subtypes demonstrated potentially altered processing, attention to and/or recognition of faces and their expressions.

This review highlights several methodological challenges involved in research on aging, health, and mortality in adults with rare intellectual disability syndromes. Few studies have been performed in this area, with research obstacles that include: the ascertainment of older adults with genetic versus clinical diagnoses; likelihood that adults will not receive adequate health care and referrals to genetic specialists; cohort differences related to generational and treatment effects; and increased mortality and selective survival biases. Even so, aging in Prader-Willi and Williams syndromes are reviewed as they reveal new insights into the phenotypic expression and treatment options for older adults with these disorders. The review ends with recommendations for future research that takes better advantage of genetic advances, changes in adult phenotypes, and ties across syndrome-specific research silos. Although aging in rare neurodevelopmental disorders is barely on the research landscape, the field stands to learn much from these older adults., (Copyright © 2013 Wiley Periodicals, Inc., a Wiley company.)

Over the past two decades, great strides have been made in our understandings of how genetic conditions influence behavior and how such so-called "behavioral phenotypes" influence parent and family stress and coping. In this paper, we call for expansions in two directions. First, as a field we need to go beyond behavior in our concepts of phenotypes, to also include the many medical, physical, and other "non-behavioral" phenotypes that influence children's everyday lives. Second, in examining how etiology-related phenotypes affect others, we need to go beyond the outcome of parental stress. In this regard, we focus on parental health, well-being, and various life choices, as well as how parenting children with specific genetic disorders can often lead to positive perceptions and outcomes. We end by discussing remaining research issues and how these two expansions relate to clinical practice.

Background: Williams syndrome (WS) is a rare genetic disorder caused by the deletion of approximately 25 genes at 7q11.23 that involves mild to moderate intellectual disability (ID). When using functional magnetic resonance imaging (fMRI) to compare individuals with ID to typically developing individuals, there is a possibility that differences in IQ contribute to between-group differences in BOLD signal. If IQ is correlated with BOLD signal, then group-level analyses should adjust for IQ, or else IQ should be matched between groups. If, however, IQ is not correlated with BOLD signal, no such adjustment or criteria for matching (and exclusion) based on IQ is necessary., Methods: In this study, we aimed to test this hypothesis systematically using four extant fMRI datasets in WS. Participants included 29 adult subjects with WS (17 men) demonstrating a wide range of standardized IQ scores (composite IQ mean = 67, SD = 17.2). We extracted average BOLD activation for both cognitive and task-specific anatomically defined regions of interest (ROIs) in each individual and correlated BOLD with composite IQ scores, verbal IQ scores and non-verbal IQ scores in Spearman rank correlation tests., Results: Of the 312 correlations performed, only six correlations (2%) in four ROIs reached statistical significance at a P value < 0.01, but none survived correction for multiple testing. All six correlations were positive. Therefore, none supports the hypothesis that IQ is negatively correlated with BOLD response., Conclusions: These data suggest that the inclusion of subjects with below normal IQ does not introduce a confounding factor, at least for some types of fMRI studies with low cognitive load. By including subjects who are representative of IQ range for the targeted disorder, findings are more likely to generalize to that population.

Deformation-based morphometry (DBM) is a widely used method for characterizing anatomical differences across groups. DBM is based on the analysis of the deformation fields generated by nonrigid registration algorithms, which warp the individual volumes to a DBM atlas. Although several studies have compared nonrigid registration algorithms for segmentation tasks, few studies have compared the effect of the registration algorithms on group differences that may be uncovered through DBM. In this study, we compared group atlas creation and DBM results obtained with five well-established nonrigid registration algorithms using 13 subjects with Williams syndrome and 13 normal control subjects. The five nonrigid registration algorithms include the following: (1) the adaptive bases algorithm, (2) the image registration toolkit, (3) The FSL nonlinear image registration tool, (4) the automatic registration tool, and (5) the normalization algorithm available in Statistical Parametric Mapping (SPM8). Results indicate that the choice of algorithm has little effect on the creation of group atlases. However, regions of differences between groups detected with DBM vary from algorithm to algorithm both qualitatively and quantitatively. Some regions are detected by several algorithms, but their extent varies. Others are detected only by a subset of the algorithms. Based on these results, we recommend using more than one algorithm when performing DBM studies., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Begun in the late 1990s, mental health courts are specialty criminal courts developed to address the needs of persons with mental illness., Methods: As many persons with intellectual disabilities (IDs) may overlap in the mental health court system, we used mental health court records to examine the phenomenology and outcomes of 224 defendants with and without co-occurring IDs in the mental health court. This study had two goals: (1) to examine the prevalence of defendants with IDs in the court and (2) to compare defendants with dual diagnoses with defendants with lone mental health disorders., Results: Approximately 11% of defendants in the mental health court also had IDs. Compared with individuals with mental health disorders alone, individuals with dual diagnoses were more likely to be younger, male, African-American and less well-educated; these defendants were also more likely to show externalising, 'turning-against-others' symptoms, less likely to show internalising, 'turning-against-self' symptoms. Defendants with IDs (vs. those without) more often received behavioural, vocational rehabilitation and other services, although the two groups did not differ on most outcome variables., Conclusion: Directions for future research are discussed., (© 2011 The Authors. Journal of Intellectual Disability Research © 2011 Blackwell Publishing Ltd.)

Purpose: Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are complex neurodevelopmental disorders caused by loss of expression of imprinted genes from the 15q11-q13 region depending on the parent of origin. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) kits from MRC-Holland (Amsterdam, The Netherlands) were used to detect PWS and AS deletion subtypes. We report our experience with two versions of the MS-MLPA-PWS/AS kit (original A1 and newer B1) in determining methylation status and deletion subtypes in individuals with PWS., Methods: MS-MLPA analysis was performed on DNA isolated from a large cohort of PWS subjects with the MS-MLPA-PWS/AS-A1 and -B1 probe sets., Results: Both MS-MLPA kits will identify deletions in the 15q11-q13 region but the original MS-MLPA-A1 kit has a higher density of probes at the telomeric end of the 15q11-q13 region, which is more useful for identifying individuals with atypical deletions. The newer B1 kit contains more probes in the imprinting center (IC) and adjoining small noncoding RNAs useful in identifying small microdeletions., Conclusion: The A1 kit identified the typical deletions and smaller atypical deletions, whereas the B1 kit was more informative for identifying microdeletions including the IC and SNORD116 regions. Both kits should be made available for accurate characterization of PWS/AS deletion subtypes as well as evaluating for IC and SNORD116 microdeletions.

Diffusion tensor imaging (DTI) was used to investigate the involvement of brain white matter in Williams syndrome (WS), a genetic neurodevelopmental disorder. Whole-brain DTIs were obtained from 16 young adults with WS and 16 normal controls. A voxel-based analysis was performed to compare fractional anisotropy (FA) values between the two groups. A tract-based analysis was also performed to compare FA values between the two groups along two major white matter tracts that pass through the external capsule: the uncinate and inferior fronto-occipital fasciculi. Several regions of both increased and decreased FA were found within major white matter tracts that connect functional regions that have previously been implicated in the cognitive and neurological symptoms of the syndrome. The tract-based analysis provided additional insight into the involvement of specific white matter tracts implicated in the voxel-based analysis within the external capsule. The results from this study support previously reported changes in white matter diffusion properties in WS and demonstrate the potential usefulness for tract-based analysis in future studies of the disorder., (Copyright © 2011 Elsevier Inc. All rights reserved.)